SAFARI Surprise: No Survival or Bleeding Advantage With Radial Over Femoral Access in STEMI
The underpowered trial won’t change things for some proponents of radial PCI, but other operators were reassured and relieved by the results.
NEW ORLEANS, LA—Operators performing PCI via the femoral artery can rest assured that the procedure causes no more harm than primary PCI performed via the radial artery, according to the results of a new study.
Presenting the SAFARI-STEMI findings at the American College of Cardiology 2019 Scientific Session, investigators reported that 30-day mortality with femoral-access PCI was no different when compared with primary PCI via the radial artery.
Rates of reinfarction, stroke, and a combined endpoint of death, reinfarction, or stroke were also no different between the two primary PCI approaches. Surprisingly, the risk of bleeding, which has been a major selling point for radial access, was not significantly lower when compared with patients treated via the femoral artery. No matter what definition of bleeding was used—TIMI major, TIMI minor, BARC 3-5, or the need for transfusion—femoral access was equivalent with radial-access PCI.
Interpreting the new data, which run counter to previous studies like RIVAL, MATRIX, RIFLE-STEACS showing that transradial PCI is associated with a lower risk of bleeding and lower mortality in STEMI patients, remains challenging given that the study was underpowered after it was stopped early for futility. Nonetheless, lead investigator Michel Le May, MD (University of Ottawa Heart Institute, Canada), said their findings suggest that adequately trained operators should be able to achieve similar results after either radial or femoral access for PCI.
“We were lucky to get as many patients as we did in this study,” Le May told TCTMD. “Most people think, seriously, the horse is out of the barn and it’s game over for femoral. There is a mindset out there where people think it’s just wrong to do the femoral approach.” They even received feedback suggesting that it’s not even ethical to randomize STEMI patients to one of the two vascular access routes.
Martin Leon, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), who chaired the late-breaking clinical trials session, said he’s been “tortured” for the last 5 years by his junior interventional colleagues who argue that “unless you’re doing transradial for STEMI, for instance, you’re not only out of step with the modern PCI era, but you’re moving against the evidence.”
Instead, the present study suggests that interventional cardiologists should aspire to be better transfemoral operators, and if they do, there really isn’t much of a difference between the two approaches, said Leon.
Claire Duvernoy, MD (University of Michigan, Ann Arbor), who trained as a transfemoral operator, made a similar comment, calling the results a “relief” and “reassuring.” While she opts for the radial artery with elective patients, when time is critical with STEMI cases, “my first instinct is still to use femoral access.”
SAFARI-STEMI trial Stopped for Futility
SAFARI-STEMI was stopped early by the Data Safety and Monitoring Board after a lower than expected rate of the primary outcome. The study was initially designed to include 4,884 patients—2,442 patients each in the femoral and radial arms—and powered to detect a 1.5% difference in the 30-day mortality rate between the two treatment groups (with an expected 30-day mortality rate of 4.0% in the femoral-access arm). In the end, just 2,292 STEMI patients were randomized, including 1,136 to radial-access PCI and 1,156 to femoral-access PCI.
When the trial was designed, investigators aimed to maximize “best practices” for the femoral and radial approaches, said Le May. This included the use of unfractionated heparin prior to PCI, loading patients with ticagrelor (91.5%), and the use of smaller sheaths. During the procedure, bivalirudin was used in the majority of patients and glycoprotein IIb/IIIa inhibitors were discouraged during PCI. A vascular closure device was used in 68.2% of those treated via femoral access.
Overall, the 30-day mortality rate was 1.3% in the transfemoral arm and 1.5% in the radial-access group, a nonsignificant difference. There was no benefit in any subgroup. During the presentation, Le May presented data from an updated meta-analysis that included SAFARI-STEMI and those results showed a lower risk of mortality among STEMI patients treated with radial access, pointing out the relative benefit approached unity (RR 0.78; 95% CI 0.61-0.99).
Although some were encouraged by SAFARI-STEMI, Sunil Rao, MD (Duke University Medical Center, Durham, NC), an advocate for transradial access, said the trial’s early stoppage makes it impossible to draw any firm conclusions.
“While this underpowered trial showed no difference between radial and femoral, it is not clear whether the really good outcomes with femoral access seen in the trial can be achieved in clinical practice,” he told TCTMD. “It’s clear from registry data that there is room for significant improvement in femoral access technique. Taken together with the vast body of data supporting radial access across the spectrum of patients undergoing PCI, transradial PCI should be the preferred approach, and if it’s not feasible then best femoral access using ultrasound guidance should be the alternative.”
Like Rao, Sanjit Jolly, MD (Hamilton General Hospital/Population Health Research Institute, Canada), cautioned against overinterpreting SAFARI-STEMI given that it enrolled only half of patients planned for the trial. “If you only have 50% power, if there is a true effect, it’s like flipping a coin,” he told TCTMD. “An underpowered trial that doesn’t show a difference is technically not a negative trial. It didn’t have sufficient power to test the hypothesis. That’s wearing a trialists’ hat and not [speaking] as a clinician.”
From a clinical perspective, Jolly pointed out that transradial volume is a predictor of clinical outcomes and it will be important to stratify the results by center/operator expertise with the radial approach. “This is not like a drug,” he said. “Both femoral and radial access are procedures and it depends on the operator, the operator’s technique, and their skill level. It’s not surprising necessarily that the results are not the same with different operators in different trials.”
On the whole, though, Jolly said the preponderance of evidence still supports radial access for PCI in STEMI patients, as shown in several meta-analyses, including the one conducted by the SAFARI-STEMI researchers. “It’s unlikely radial access is going to reduce mortality by 50%, as was shown in some of the smaller trials and the RIVAL analysis,” he said. The relative reduction in 30-day mortality with transfemoral PCI in STEMI is more likely to smaller, somewhere around 20%, said Jolly.
Speaking with the media, Duvernoy said that the use of bivalirudin and closure devices are not standard practice at her hospital, and as such, extrapolating the results remain a challenge. Roxana Mehran, MD (Icahn School of Medicine at Mount Sinai, New York, NY), agreed, noting that bivalirudin reduces the risk of bleeding, although most labs are simply using unfractionated heparin. For this reason, she’s uncertain if the bleeding results are applicable to the real world.
Achieving Excellent Results With Transfemoral PCI
In a discussion following the late-breaking trial’s presentation, Rao asked how transfemoral operators in the real world can achieve clinical outcomes as good as those observed in the SAFARI-STEMI. Le May, for his part, said the emergence and championing of transradial PCI has forced interventional cardiologists to be better when performing PCI via the femoral artery.
“We have to pay attention to their puncture,” said Le May. “We use fluoroscopic guidance and there are people who use ultrasound. We pay attention to anticoagulation and antiplatelet therapy in these patients. We use less GP IIb/IIIa inhibitors and smaller sheaths. We’ve also borrowed some of the techniques radial-access people use. We have become better at knowing the radial and femoral access approaches.”
Speaking with TCTMD, Ashish Pershad, MD (Banner-University Medical Center, Phoenix, AZ), said SAFARI-STEMI showed that the transfemoral approach has matured, which he attributes to physicians performing more large-bore access cases. With TAVR and use of devices such as Impella (Abiomed), physicians are better at managing the femoral artery for access.
“Our overall quality of femoral access has improved nationally, and even though [SAFARI-STEMI] could be replicated, I don’t think this is an indication we should go back in time, back doing only cases with the femoral artery,” said Pershad. “Ultimately, patient preference dictates a lot of what happens. And I think to show a difference in clinical outcomes would require a 10,000-patient trial. I still believe a bleeding-avoidance approach with a transradial approach is the correct approach to the problem.”
Le May MR, Wells GA, So, DY, et al. The safety and efficacy of femoral access vs radial access in STEMI. Presented at: ACC 2019. March 18, 2019. New Orleans, LA.
- Le May, Rao, and Jolly reports no conflicts of interest.